Lung cancer represents the most frequent form of malignancy comprising about 25% of all cancer clinical cased worldwide and being one of few cancer types with steadily increasing occurence. Non-small cell lung carcinomas (NSCLC) are proven to be challenging tumor type for clinical management with frequent re-occurrence of drug resistant cancer after initial surgery/therapy and prominent metastatic potential. To gain in-depth insight into the molecular basis of lung carcinoma formation and reasons for drug resistance in relapse phase, the Center for Advanced Preclinical Research successfully adopted and characterized several models of NSCLC. We have recently successfully completed several studies with a Biotechnology Company that established the utility of their irreversible EGFR inhibitor in the regression of LA harboring the primary L858R EGFR mutant present in patient cancers and of those resistant to first line therapy that express the L858RT790 mutant. We completed preclinical studies of a proprietary agent, including PK/PD/Tox and efficacy evaluation, in collaboration with a pharmaceutical company. We have also initiated an intramural collaboration aimed at efficacy testing of several photosensitizing agents in RTK-driven lung cancer models.